Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: WAC

Gene summary for WAC

Gene summary.

Gene information	Species	Human
	Gene symbol	WAC
	Gene ID	51322
	Gene name	WW domain containing adaptor with coiled-coil
	Gene Alias	BM-016
	Cytomap	10p12.1
	Gene Type	protein-coding
	GO ID	GO:0000075
	UniProtAcc	Q9BTA9

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
51322	WAC	CA_HPV_1	Human	Cervix	CC	1.14e-06	-6.65e-02	0.0264
51322	WAC	CCI_1	Human	Cervix	CC	1.16e-04	8.37e-01	0.528
51322	WAC	CCI_2	Human	Cervix	CC	1.16e-07	1.19e+00	0.5249
51322	WAC	CCI_3	Human	Cervix	CC	1.36e-08	8.37e-01	0.516
51322	WAC	L1	Human	Cervix	CC	2.71e-03	-2.29e-01	0.0802
51322	WAC	HTA11_3410_2000001011	Human	Colorectum	AD	1.13e-21	-6.27e-01	0.0155
51322	WAC	HTA11_1938_2000001011	Human	Colorectum	AD	6.84e-04	4.80e-01	-0.0811
51322	WAC	HTA11_347_2000001011	Human	Colorectum	AD	4.17e-05	3.81e-01	-0.1954
51322	WAC	HTA11_99999965062_69753	Human	Colorectum	MSI-H	2.63e-04	8.29e-01	0.3487
51322	WAC	HTA11_99999965104_69814	Human	Colorectum	MSS	5.25e-08	5.98e-01	0.281
51322	WAC	HTA11_99999974143_84620	Human	Colorectum	MSS	6.48e-06	-4.08e-01	0.3005
51322	WAC	A001-C-207	Human	Colorectum	FAP	2.54e-04	-1.50e-01	0.1278
51322	WAC	A015-C-203	Human	Colorectum	FAP	4.61e-34	-3.28e-01	-0.1294
51322	WAC	A015-C-204	Human	Colorectum	FAP	1.28e-07	-2.69e-01	-0.0228
51322	WAC	A014-C-040	Human	Colorectum	FAP	1.45e-06	-3.98e-01	-0.1184
51322	WAC	A002-C-201	Human	Colorectum	FAP	4.30e-14	-2.96e-01	0.0324
51322	WAC	A002-C-203	Human	Colorectum	FAP	1.22e-03	-1.48e-01	0.2786
51322	WAC	A001-C-119	Human	Colorectum	FAP	2.35e-05	-2.70e-01	-0.1557
51322	WAC	A001-C-108	Human	Colorectum	FAP	7.60e-15	-2.23e-01	-0.0272
51322	WAC	A002-C-205	Human	Colorectum	FAP	1.13e-27	-3.87e-01	-0.1236

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Cervix		CC: Cervix cancer
		HSIL_HPV: HPV-infected high-grade squamous intraepithelial lesions
		N_HPV: HPV-infected normal cervix
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Endometrium		AEH: Atypical endometrial hyperplasia
		EEC: Endometrioid Cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:00459303	Prostate	BPH	negative regulation of mitotic cell cycle	60/3107	235/18723	3.00e-04	2.32e-03	60
GO:00162416	Prostate	BPH	regulation of macroautophagy	40/3107	141/18723	3.09e-04	2.37e-03	40
GO:00315716	Prostate	BPH	mitotic G1 DNA damage checkpoint	13/3107	30/18723	5.11e-04	3.62e-03	13
GO:00448196	Prostate	BPH	mitotic G1/S transition checkpoint	13/3107	31/18723	7.48e-04	4.95e-03	13
GO:19019874	Prostate	BPH	regulation of cell cycle phase transition	89/3107	390/18723	8.17e-04	5.34e-03	89
GO:19028072	Prostate	BPH	negative regulation of cell cycle G1/S phase transition	28/3107	93/18723	8.54e-04	5.53e-03	28
GO:19019913	Prostate	BPH	negative regulation of mitotic cell cycle phase transition	46/3107	179/18723	1.24e-03	7.51e-03	46
GO:00165745	Prostate	BPH	histone ubiquitination	16/3107	47/18723	2.71e-03	1.44e-02	16
GO:00065134	Prostate	BPH	protein monoubiquitination	20/3107	67/18723	4.93e-03	2.33e-02	20
GO:00162392	Prostate	BPH	positive regulation of macroautophagy	19/3107	63/18723	5.36e-03	2.49e-02	19
GO:004217619	Prostate	Tumor	regulation of protein catabolic process	142/3246	391/18723	9.32e-20	5.79e-17	142
GO:001049819	Prostate	Tumor	proteasomal protein catabolic process	158/3246	490/18723	3.05e-16	6.76e-14	158
GO:000989619	Prostate	Tumor	positive regulation of catabolic process	155/3246	492/18723	5.62e-15	8.52e-13	155
GO:190336219	Prostate	Tumor	regulation of cellular protein catabolic process	95/3246	255/18723	1.92e-14	2.54e-12	95
GO:190305019	Prostate	Tumor	regulation of proteolysis involved in cellular protein catabolic process	83/3246	221/18723	5.12e-13	5.49e-11	83
GO:003133119	Prostate	Tumor	positive regulation of cellular catabolic process	134/3246	427/18723	5.54e-13	5.84e-11	134
GO:004316119	Prostate	Tumor	proteasome-mediated ubiquitin-dependent protein catabolic process	130/3246	412/18723	7.97e-13	8.00e-11	130
GO:200005819	Prostate	Tumor	regulation of ubiquitin-dependent protein catabolic process	66/3246	164/18723	3.30e-12	2.78e-10	66
GO:006113619	Prostate	Tumor	regulation of proteasomal protein catabolic process	71/3246	187/18723	1.34e-11	1.00e-09	71
GO:003243419	Prostate	Tumor	regulation of proteasomal ubiquitin-dependent protein catabolic process	55/3246	134/18723	8.40e-11	5.27e-09	55

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

WAC

SNV

Missense_Mutation

c.306C>G

p.His102Gln

p.H102Q

Q9BTA9

protein_coding

tolerated(0.13)

benign(0.063)

TCGA-A2-A3XT-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cyclophosphamide

WAC

SNV

Missense_Mutation

c.1142N>C

p.Val381Ala

p.V381A

Q9BTA9

protein_coding

deleterious(0.03)

possibly_damaging(0.503)

TCGA-A8-A06X-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

novel

c.1798N>A

p.Glu600Lys

p.E600K

Q9BTA9

protein_coding

tolerated(0.09)

probably_damaging(0.972)

TCGA-AN-A046-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

novel

c.16A>G

p.Arg6Gly

p.R6G

Q9BTA9

protein_coding

deleterious(0.04)

benign(0)

TCGA-AQ-A7U7-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Targeted Molecular therapy

rituximab

WAC

SNV

Missense_Mutation

rs200723559

c.1586N>G

p.Asn529Ser

p.N529S

Q9BTA9

protein_coding

tolerated(0.13)

possibly_damaging(0.584)

TCGA-BH-A0E0-01

Breast

breast invasive carcinoma

Female

<65

III/IV

Chemotherapy

docetaxel

WAC

SNV

Missense_Mutation

rs750794271

c.376N>C

p.Asp126His

p.D126H

Q9BTA9

protein_coding

deleterious(0.01)

probably_damaging(0.995)

TCGA-D8-A27G-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

WAC

SNV

Missense_Mutation

c.1887N>C

p.Leu629Phe

p.L629F

Q9BTA9

protein_coding

deleterious(0)

probably_damaging(0.991)

TCGA-E2-A10C-01

Breast

breast invasive carcinoma

Female

<65

I/II

Chemotherapy

cytoxan

WAC

SNV

Missense_Mutation

c.1595C>A

p.Ser532Tyr

p.S532Y

Q9BTA9

protein_coding

tolerated(1)

possibly_damaging(0.598)

TCGA-GM-A2D9-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

WAC

insertion

Frame_Shift_Ins

novel

c.1537_1538insT

p.Arg513LeufsTer8

p.R513Lfs*8

Q9BTA9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

WAC

insertion

Frame_Shift_Ins

novel

c.1538_1539insAGGGAGAATTATTAATCATATCCCCTCACCCCACCAA

p.Ser514GlyfsTer19

p.S514Gfs*19

Q9BTA9

protein_coding

TCGA-A2-A0EO-01

Breast

breast invasive carcinoma

Female

<65

I/II

Hormone Therapy

tamoxiphen

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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